RF signals provide additional information on embolic events recorded during TCD monitoring

Transcranial Doppler ultrasound (TCD) is commonly used to detect embolic signals in the cerebral circulation. However, current techniques to discriminate between signals from emboli and artifacts are subjective and ambiguous. The radiofrequency (RF) signal provides an extra dimension to the information available from conventional TCD systems that may help to interpret complex events. Artifacts generated by healthy volunteers and embolic signals recorded from a flow phantom were used to characterize the appearance of the two types of event. Characteristics of events, recorded during and immediately after carotid endarterectomy surgery, were compared with those from known sources. Additional information was provided by the RF signal on events recorded during TCD monitoring thus aiding classification. The RF signal may have a role as a "gold standard" for embolus detection.     

Dynamic resolution selection in ultrasonic strain imaging

Ultrasonic strain imaging promises to be a valuable tool in medical diagnostics. Reliability and ease-of-use have become important considerations. These depend on selection of appropriate imaging parameters. Two tasks are undertaken here. The tradeoff between resolution and estimation precision is examined closely to establish models for the relationships with imaging parameters and data properties. These models are then applied in a system that automatically sets the imaging parameters responsive to the data quality and the required estimation precision, so as to produce more meaningful images under varying scan conditions. The new system is applied to simulation, in vitro and in vivo data for validation. It reduces the complexity of the sonographer's role in strain imaging, and produces images of reliable quality even when the level of signal decorrelation varies throughout the ultrasound data. (E-mail: jel35@eng.cam.ac.uk)     

Subsample interpolation strategies for sensorless freehand 3D ultrasound

Freehand 3D ultrasound can be acquired without a position sensor by deducing the elevational probe motion from the interframe speckle decorrelation. However, a freehand scan involves lateral and axial, as well as elevational, probe motion. The lateral sampling is determined by the A-line separation and is relatively sparse: lateral motion tracking therefore requires subsample interpolation. In this paper, we investigate the resilience of lateral interpolation techniques to simultaneous lateral and elevational probe motion. We propose a novel interpolation strategy and, through a series of in vitro experiments, compare its performance with that of established alternatives. The new technique is shown to be superior, limiting interpolation errors to around 5% of the length of the freehand reconstruction. (E-mail: rjh80@eng.cam.ac.uk)     

A novel method to measure acoustic speed of bone tissue

Acoustic speed is an important parameter that can be used to characterize bone tissue for evaluation of osteoporosis. Traditional approaches for measuring acoustic speed require knowledge of either the specimen thickness, which is sometimes difficult to obtain from biological tissues, or the reference fluid velocity that, moreover, is an unknown parameter for internal tissue in in vivo measurement. In this paper, a new method is proposed to measure acoustic speed from dual reflected ultrasound signals. This technique utilizes two transducers placed on the same side of the test object; one for transmitter and receiver, and the other one for receiver only. The acoustic speed of the test object is based on the information of time-of-flight from the signals received by both transducers and the separation distance between the transducer pair. The technique developed here not only eliminates the requirement of knowledge of specimen thickness, but also shows a feasibility for clinical applications. The results of different porcine and bovine bone samples measured in vitro by this technique are in good agreement with those measured by other published methods. In vivo measurement results of 10 healthy young volunteers' tibias are also reported.     

Detection of Doppler embolic signals: psychoacoustic considerations

The purpose of this study was to improve reliability in the identification of Doppler embolic signals by determining the decibel threshold for reproducible detection of simulated "emboli" as a function of signal duration, frequency and cardiac-cycle position. The auditory sensitivity of 16 participants to 574 simulated "emboli" was examined using psychoacoustic techniques to assess how the probability of detection varies with embolic signal parameters. Detailed measurements of the threshold for detection of simulated embolic signals are presented. These provide evidence that the measured embolus-to-blood threshold ranges between 2 dB and 14 dB as a continuous function of signal duration and frequency. The level of the threshold is closely linked to both embolic signal parameters and the properties of the blood flow signal. We conclude that the current fixed choice of threshold does not provide a good approximation to the true threshold of detection across the full range of embolic signal parameters.     

Frequency filtering improves ultrasonic embolic signal detection.

Problems in detection of Doppler cerebral embolic signals primarily occur for embolic signals of low relative intensity. A characteristic feature of embolic signals is that the intensity increase is maximal over a narrow frequency band. Therefore, frequency filtering of the data might improve embolic signal relative intensity and detectability. We implemented an off-line finite impulse response filter in software running on a commercially available transcranial Doppler system, using the time-domain audio data as input. The range of the filter was chosen by placing a box around the embolic signal on the spectral display. One hundred consecutive embolic signals from patients with carotid stenosis were analyzed; all had been recorded by a bigate system and the signal was analyzed in both proximal and distal channels. There was a highly significant increase in embolic signal relative intensity following frequency filtering; mean (SD) proximal channel prefiltering 12.75 (4.83) dB, postfiltering 16.36 (4.93) dB; distal channel prefiltering 13.42 (4.98) dB, postfiltering 16.60 (5.11) dB, for both p < 0.001. Despite all embolic signals being audible and visible in at least one channel on the frequency spectral display, in 17 cases, the amplitude increase associated with the embolic signal could not be clearly seen in time-domain data of one or both channels prior to filtering. Following frequency filtering, this was reduced to 5. Incorporation of such a frequency-filtering approach to an online system is likely to improve the sensitivity of online detection for embolic signals of low relative intensity.     

Optimization of processing parameters for the analysis and detection of embolic signals.

The fast Fourier transform (FFT), which is employed by all commercially available ultrasonic systems, provides a time-frequency representation of Doppler ultrasonic signals obtained from blood flow. The FFT assumes that the signal is stationary within the analysis window. However, the presence of short duration embolic signals invalidates this assumption. For optimal detection of embolic signals if FFT is used for signal processing, it is important that the FFT parameters such as window size, window type, and required overlap ratio should be optimized. The effect of varying window type, window size and window overlap ratio were investigated for both simulated embolic signals, and recorded from patients with carotid artery stenosis. An optimal compromise is the use of a Hamming or Hanning window with a FFT size of 64 (8.9 ms) or 128 (17.9 ms). A high overlap ratio should also be employed in order not to miss embolic events occurring at the edges of analysis windows. The degree of overlap required will depend on the FFT size. The minimum overlap should be 65% for a 64-point window and 80% for a 128-point window.     

Real-time software processing and audio reproduction of directional Doppler signals

In ultrasound Doppler systems, directional signals are typically obtained by processing quadrature demodulated data with dedicated analog or digital circuits. In this paper, a software approach is proposed, that allows fully exploiting the reproduction and recording capabilities of low-cost personal computer sound cards and/or embedded chips. Forward/reverse signals are separated through a wideband Hilbert filter. No limitations are imposed on the input signal sample rate, which is matched to the standard output format of sound cards through a band-limited interpolation filter controlled in a feedback loop. The digital audio streaming is performed in real-time in a Windows®-based application. The processed data are in a standard format compatible with real-time recording in waveform or compressed files, as requested in many research applications. Simulations and in vivo tests show a typical cross talk of −50 dB between forward and reverse components, with low latency time (39 ms) and central processing unit load compatible to currently available personal computers. (E-mail: piero.tortoli@unifi.it)     

Quantification of Embolic Showers Using Radio-Frequency Based TCD Analysis

During cardiac surgery and cardiology interventions, microemboli may be generated and disperse in the systemic circulation. The amount of microemboli that ends up in cerebral blood vessels is associated with postoperative neurologic complications. During cardiac surgery a large amount of cerebral microemboli can occur at once and create so-called “cerebral embolic showers.” To correlate postoperative neurologic outcome to cerebral embolic load, a quantitative evaluation of these embolic showers is necessary. The standard monitoring technology to visualize cerebral microemboli is transcranial Doppler (TCD). Although the conventional TCD systems are equipped with software claiming to detect microembolic signals, none of the existing TCD systems is capable of an accurate estimation of the number of cerebral microemboli in embolic showers. In this study, an algorithm with a high temporal resolution, based on the radiofrequency (RF) signal of a TCD system, has been designed to quantify these showers. Evaluation by three independent observers of a training set demonstrates that the proposed method has a sensitivity of at least one order of magnitude better than the automatic detection algorithm on the existing Doppler device used. RF-based emboli detection can possibly become a standard addition to conventional Doppler methods, considering that accurate estimation of the embolic load supports quantification of neurologic risk during various surgical procedures. (E-mail: l.sauren@ctc.unimaas.nl)     

Analysis of the photoplethysmographic signal by means of the decomposition in principal components

We study the plethysmographic signal using principal component analysis (PCA). By decomposing the signal using this method, we are able to regenerate it again, preserving in the process the functional relationships between the components. We have also found the relative contributions of each specific component to the signal. First return maps have been made for the series of residues of the decomposition. Further analysis using spectral methods has shown that the residues have a 1/f -like structure, which confirms the presence and conservation of this component in the signal and its relative independence with respect to the oscillating component (Hernández et al 2000 Rev. Cubana Inform. Medica 1 5). Our conclusions are that: (i) PCA is a good method to decompose the plethysmographic signal since it preserves the functional relationships in the variables, and this could be potentially useful in finding new clinically relevant indices; (ii) the 1/f process of the plethysmographic signal is preserved in the residues of the decomposed signal when PCA is used; (iii) clinically relevant parameters can potentially be obtained from photoplethysmographic signals when PCA is used.     

Experimental verification of the correlation behavior of analytic ultrasound radiofrequency signals received from moving structures

Conventional pulsed ultrasound systems are only able to detect motion along the ultrasound beam (i.e., axial motion). If the angle between the actual motion direction and the ultrasound beam is known, then the magnitude of the actual motion can be derived. This technique can be applied for laminar blood-flow measurements in straight vessels, but for tissue motion it is inadequate because the local tissue motion direction is unknown and may be position-dependent. Assessment of both the axial motion and the lateral motion (i.e., in the direction perpendicular to the ultrasound beam) makes angle-independent assessment of the magnitude of the actual motion feasible. Information about the axial and lateral motion is available in a set of radiofrequency (RF) signals obtained along the same line of observation (M-mode). The experiments described in the present paper show that axial and lateral motion can be estimated from the shape of the envelope of the 2-D (spatial and temporal) correlation function of analytic M-mode RF signals. Furthermore, it is demonstrated that the shape is also affected by the Band width of the received RF signals, signal-to–noise ratio, and local amplitude and phase characteristics of the ultrasound beam.     

In vivo kinetics of microbubbles of SH U 508 A (Levovist): comparison with indocyanine green in rabbits

The aim of this study was to evaluate in vivo kinetics of microbubbles of SH U 508 A, in comparison with Indocyanine Green, a dye used as an indicator of blood flow. Microbubble kinetics were evaluated in various vessels (i.e., vena cava, aorta, renal artery, renal vein and portal vein) in rabbits after injection of SH U 508 A by measuring Doppler signals (n = 5). The kinetics of Indocyanine Green were evaluated by measuring absorbance using a photodiode (n = 5). Test substances (SH U 508 A 300 mg/mL and Indocyanine Green 1.25 mg/mL) were injected IV at a dose of 0.1 mL/kg B.W. Peak signal intensity was observed immediately after injection of SH U 508 A, followed by biphasic decay. The rates of biphasic decay were similar in all vessels. A second peak of the signal, which indicated recirculation of the microbubbles, was observed in the vena cava. The circulation and recirculation times of the microbubbles after injection of SH U 508 A were similar to that of Indocyanine Green. These findings suggest that the majority of SH U 508 A microbubbles circulate through the body similarly to blood flow, without retention, in the vasculature.     

Characteristics of Doppler embolic signals observed following carotid endarterectomy

Postoperative Doppler embolic signals following carotid endarterectomy (CEA) are associated with an increased risk of stroke, but the characteristics of these signals are rarely reported. In this study, we survey signals from 1485 emboli, assumed to consist predominantly of thrombus. Data were obtained by monitoring the middle cerebral arteries of 100 consecutive CEA patients during postoperative recovery. The distribution of embolic signal frequencies, intensities and durations revealed that embolic signals do not occur randomly in the sonogram. In particular, we find that the signals possess a characteristic distribution of velocities reflecting the preferred path of the embolus through the artery (at approximately 75% of the distance between the centre of the artery and the artery wall). Embolic signals were more likely to be observed at cardiac cycle positions between 35% and 80% from the start of systole than elsewhere. After eliminating other considerations, we hypothesized that this peak in the distribution of signals in the sonogram arose due to the localization of emboli trajectories and a strong tendency for emboli to detach from the carotid bifurcation during systole.     

Subharmonic contrast intravascular ultrasound for vasa vasorum imaging

The feasibility of subharmonic contrast intravascular ultrasound (IVUS) imaging was investigated using a prototype nonlinear IVUS system and the commercial contrast agent Definity™. The system employed a mechanically scanned commercial catheter with a custom transducer element fabricated to have sensitivity at both 15 and 30 MHz. Experiments were conducted at a fundamental frequency of 30 MHz (F30; 25% bandwidth), with on-axis pressures ranging from 0.12 to 0.79 MPa, as measured with a needle hydrophone. In vitro characterization experiments demonstrated the detection of 15 MHz subharmonic signals (SH15) when pressure levels reached 360 kPa. The formation of SH15 images was shown, with tissue signals suppressed to near the noise floor and contrast to tissue ratios were improved by up to 30 dB relative to F30. In vivo experiments were performed using the atherosclerotic rabbit aorta model. Following the bolus injection of contrast agent upstream of the imaging catheter, agent was detected within the aorta, vena cava and within the perivascular space. These results provide a first in vivo demonstration of subharmonic contrast IVUS and suggest its potential as a new technique for imaging vasa vasorum. (E-mail: goertz@sri.utoronto.ca)     

Doppler indices in the umbilical arteries: influence of vessel curvature induced by bladder filling

Doppler indices are widely used to assess normal versus pathologic haemodynamics. In obstetrics, the assessment of abnormal values in some critical compartments, such as the umbilical arteries (UA), may be crucial in the clinical management of growth-restricted foetuses. It was recently proposed that the UA should be sampled in their perivesical portion (PVC), i.e., where they surround the foetal urinary bladder. However, measurements at this site could be biased by the degree of curvature of the vessel due to bladder filling. We investigated this possibility in vivo and in vitro, i.e., measurements on rubber tubes at different radii of curvature R_c. There was significant dependence of the Doppler indices A/B and PI on the vessel curvature and insonation angle; in fact, we recorded errors of about 25% when R_c was 10 times larger than the radius of the vessel and about 100% when R_c was five times larger than the radius of the vessel. Therefore, measurements of the UA at the PVC site should only be performed when the foetal bladder is empty. (E-mail: caterina.guiot@unito.it)     

Comparison of the performance of the RF cross correlation and doppler autocorrelation technique to estimate the mean velocity of simulated ultrasound signals

In pulsed Doppler systems the received RF (radio frequency) signal is multiplied by a quadrature reference signal and subsequently averaged over a short depth range to obtain a sample of the complex Doppler signal. The mean frequency of the sampled Doppler signal, obtained with the autocorrelation function, reflects the mean velocity of the scatterers moving through the sample volume. An alternative is to evaluate the two-dimensional cross correlation function of a short segment of the RF signals over subsequent lines, giving the mean velocity of the scatterers. Both methods of velocity estimation were applied to computer-generated RF signals with varying RF bandwidth, signal-to-noise ratio, and mean and width of the imposed velocity distribution. The length of the RF signal segment and the number of lines for velocity estimation (package length) affects the accuracy of the velocity estimate. It can be concluded that the cross correlation technique behaves superiorly especially for a low velocity dispersion. Furthermore, the standard deviation of the velocity estimate decreases for an increasing sample volume length and package length, while the performance of the conventional Doppler technique is rather independent of the length of the sample volume. The difference between both techniques decreases for a greater package length or for signals simulating a wide velocity distribution.     

The use of the wavelet transform to describe embolic signals.

A number of methods to detect cerebral emboli and differentiate them from artefacts using Doppler ultrasound have been described in the literature. In most, Fourier transform-based (FT) spectral analysis has been used. The FT is not ideally suited to analysis of short-duration embolic signals due to an inherent trade-off between temporal and frequency resolution. An alternative approach that might be expected to describe embolic signals well is the wavelet transform. Wavelets are ideally suited for the analysis of sudden short-duration signal changes. Therefore, we have implemented a wavelet-based analysis and compared the results of this with a conventional FFT-based analysis. The temporal resolution, as measured by the half-width maximum, was significantly better for the continuous wavelet transform (CWT), mean (SD) 8.40 (8.82) ms, compared with the 128-point FFT, 12.92 (9.70) ms, and 64-point FFT, 10.80 (5.69) ms. Time localization of the CWT for the embolic signal was also significantly better than the FFT. The wavelet transform appears well suited to the analysis of embolic signals offering superior time resolution and time localization to the FFT.     

Robustness of reconstructing the Young's modulus distribution of vulnerable atherosclerotic plaques using a parametric plaque model

Assessment of atherosclerotic plaque composition is crucial for quantitative monitoring of atherosclerosis and for quantifying the effect of pharmaceutical plaque-stabilizing treatments during clinical trials. We assessed this composition by applying a geometrically constrained, iterative inverse solution method to reconstruct a modulus elastogram (i.e., Young’s modulus image) from a plaque strain elastogram (i.e., radial strain image) that is measured using intravascular ultrasound strain elastography. This reconstruction method is especially suited for thin-cap fibroatheromas (TCFAs) (i.e., plaques with a thin fibrous cap overlaying a lipid pool). Because a strain elastogram of a plaque depends upon the plaque material composition, catheter position within the vessel and measurement noise, this paper investigates how robust the reconstruction is when these parameters are varied. To this end, a standard plaque was defined as the modulus elastogram that was reconstructed from an in vivo measured strain elastogram of a human coronary plaque. This standard plaque was used to computer-simulate different strain elastograms, by varying the 1. geometry and material properties of its plaque components, 2. catheter position and 3. level of added strain noise. Robustness was evaluated by quantifying the correctly reconstructed size, shape and Young’s modulus of each plaque component region and minimal cap thickness. The simulations showed that TCFAs can be adequately reconstructed; the thinner and stiffer the cap or the softer and larger the lipid pool, the better is the reconstruction of these components and minimal cap thickness. Furthermore, reconstructions were 1. independent of catheter position and 2. independent of strain noise. As such, this method has potential to monitor robustly and quantitatively atherosclerosis in vivo. (E-mail: r.baldewsing@erasmusmc.nl)     

The regulation of adenylyl cyclase by receptor-operated G proteins

The receptor regulated adenylyl cyclase system is a multiprotein complex which is a member of the family of the receptor-effector systems whose signal is transduced by heterotrimetric GTP-binding proteins. The system consists of stimulatory and inhibitory receptors (R_s and R_i), stimulatory and inhibitory G proteins (G_s and G_i) and the adenylyl cyclase enzyme (C). While quite specific in situ, receptors (stimulatory or inhibitory) from one source can activate the appropriate G protein from other cell types or species which in turn can act on C from other sources. Studies with chimeric proteins have shown that the various specificities (stimulatory or inhibitory) can be mapped to defined domains in both receptors and G proteins. The mechanism by which the heterotrimetric G proteins couple to the stimulatory and inhibitory signals is discussed in detail. Specifically, the data supporting collision coupling vs the shuttle mechanism is reviewed, as well as the role of βγ subunits in both the stimulatory and inhibitory signals.     

The wall signal removal in Doppler ultrasound systems based on recursive PCA

In Doppler ultrasound (US) systems, a high-pass filter is usually employed to remove the wall component from the blood flow signal. However, this will lead to the loss of information from the low velocity flow. In this paper, an algorithm based on the principal components analysis (PCA) is proposed, in which singular value decomposition (SVD) is used to extract the main component from the mixed signals. Furthermore, the recursive process is incorporated into the PCA method to improve the performance of wall signal removal. This approach and the traditional high-pass filtering one are, respectively, applied to analyze the computer-simulated in vitro and in vivo Doppler US signals. With the proposed method, the wall signal can be removed while a large portion of low-velocity blood signal remains. Comparison experiments show that this novel approach can satisfy the requirements of Doppler US system and is practicable under a broad range of measurement conditions. Because this algorithm is based on real data, it is currently applied to unidirectional signals.